Platelet-activating Factor (PAF) Induces Growth Stimulation, Inhibition, and Suppression of Oncogenic Transformation in NRK Cells Overexpressing the PAF Receptor

Abstract

Platelet-activating factor (PAF) is a phospholipid mediator with various physiological functions, including cellular growth and transformation. PAF exerts biological activities through G-protein-coupled receptors. In normal rat fibroblasts overexpressing a cloned PAF receptor, PAF induced immediate early oncogene expression and mitogenic responses. On the other hand, PAF strongly inhibited the epidermal growth factor-induced mitogenic growth response, growth acceleration, and anchorage-independent cell growth in a soft agar. Furthermore, PAF suppressed v-src-or v-ras-induced oncogenic morphological changes and anchorage-independent growth. Our observations suggest that PAF is a unique growth regulator with apparently diverse functions. Dual actions of PAF may relate to the point of action in the cell cycle; PAF stimulates the mitogenic response in G 0 -arrested cells in a pertussis toxin-sensitive manner, while it inhibits the G 1 to S transition through a pertussis toxin-resistant manner.

Platelet-activating Factor Mediates MMP-2 Expression and Activation via Phosphorylation of cAMP-response Element-binding Protein and Contributes to Melanoma Metastasis

“…Although an examination of the effect of PAF on cell growth was not a major objective of our study, we showed that cPAF had a weak stimulatory effect on melanoma cell growth on prolonged incubation in a serum-containing medium. This observation agrees well with other reports that have shown that in nanomolar concentrations PAF produces a weak stimulatory effect on the proliferation of human T-cells, human fibroblasts, human endometrial cancer cells, Kaposi sarcoma cells, normal rat fibroblasts, and rat primary embryo cells (45)(46)(47)(48)(49)(50). Similar to our findings in melanoma, in rat primary embryo cells, PAF promoted the ability of cells to reach a higher saturation density in a serum-containing medium (46).…”

“…2), which could be attributed to the nuclear and cytoplasmic membrane distribution of PAFR in human melanoma cells. (45)(46)(47)(48)(49)(50). To examine whether modulation of PAFR activity affects melanoma cell growth, the highly metastatic A375SM human melanoma cells were incubated with the stable and metabolically nonhydrolyzable PAF analogue, cPAF, or with the synthetic PAFR antagonist PCA4248 at various concentrations.…”

A DNA damage and stress inducible G protein-coupled receptor blocks cells in G2/M

“…Activation of the platelet-activating factor receptor can block v-Src and v-Ras induced oncogenic morphological changes and anchorage-independent growth (64). Binding of the yeast ␣-mating factor to its receptor Ste2 induces a G 1 arrest via a cyclin-dependent kinase inhibitor FAR1 (65)(66)(67).…”

Spectrum Normalization Method Using an External Standard in Mass Spectrometric Imaging

“…As a candidate, we selected methylcarbamyl platelet-activating factor (C-PAF) (C-16). 17) It has a glycerol backbone and an alkyl group connected by an ether linkage at the C1 carbon to a sixteen-carbon chain. The acyl group at the C2 carbon is modified from an acetate unit to a methyl῍carbamyl unit.…”